Structure Disulfides have a C–S–S–C
dihedral angle approaching 90°. The S–S bond length is 2.03 Å in
diphenyl disulfide, similar to that in elemental sulfur. Disulfides are usually symmetric but they can also be unsymmetric. Symmetrical disulfides are compounds of the formula . Most disulfides encountered in organosulfur chemistry are symmetrical disulfides.
Unsymmetrical disulfides (also called
heterodisulfides or
mixed disulfides) are compounds of the formula . Unsymmetrical disulfide are less common in organic chemistry, but many disulfides in nature are unsymmetrical.
Cyclic disulfides Disulfides can be components of rings.
Lipoic acid, a
1,2-dithiolane is a major example. Rings with more than one disulfide usually tend to polymerize.
Other specialized organic disulfides Thiuram disulfides, with the formula (R2NCSS)2, are disulfides but they behave distinctly because of the
thiocarbonyl group.
Properties Disulfide bonds are strong, with a typical
bond dissociation energy of 60 kcal/mol (251 kJ mol−1). However, being about 40% weaker than and bonds, the disulfide bond is often the "weak link" in many molecules. Furthermore, reflecting the
polarizability of divalent sulfur, the bond is susceptible to scission by polar reagents, both
electrophiles and especially
nucleophiles (Nu): RS-SR + Nu- -> RS-Nu + RS- The disulfide bond is about 2.05
Å in length, about 0.5 Å longer than a bond. Rotation about the axis is subject to a low barrier. Disulfides show a distinct preference for
dihedral angles approaching 90°. When the angle approaches 0° or 180°, then the disulfide is a significantly better oxidant. Disulfides where the two R groups are the same are called symmetric, examples being
diphenyl disulfide and
dimethyl disulfide. When the two R groups are not identical, the compound is said to be an asymmetric or mixed disulfide. Although the
hydrogenation of disulfides is usually not practical, the equilibrium constant for the reaction provides a measure of the standard redox potential for disulfides: :RSSR + H2 -> 2 RSH This value is about −250 mV versus the
standard hydrogen electrode (pH = 7). By comparison, the standard reduction potential for
ferrodoxins is about −430 mV.
Synthesis Disulfide bonds are usually formed from the
oxidation of
thiol () groups, especially in biological contexts. The transformation is depicted as follows: :2 RSH RS-SR + 2 H+ + 2 e- A variety of oxidants participate in this reaction including oxygen and
hydrogen peroxide. Such reactions are thought to proceed via
sulfenic acid intermediates. In the laboratory,
iodine in the presence of base is commonly employed to oxidize thiols to disulfides. Several metals, such as copper(II) and iron(III)
complexes affect this reaction. Alternatively, disulfide bonds in proteins often formed by
thiol-disulfide exchange: : RS-SR + R'SH R'S-SR + RSH Such reactions are mediated by enzymes in some cases and in other cases are under equilibrium control, especially in the presence of a catalytic amount of base. The
alkylation of alkali metal di- and
polysulfides gives disulfides. "Thiokol" polymers arise when
sodium polysulfide is treated with an alkyl dihalide. In the converse reaction, carbanionic reagents react with elemental sulfur to afford mixtures of the thioether, disulfide, and higher polysulfides. These reactions are often unselective but can be optimized for specific applications.
Synthesis of unsymmetrical disulfides (heterodisulfides) Many specialized methods have been developed for forming unsymmetrical disulfides. Reagents that deliver the equivalent of "" react with thiols to give asymmetrical disulfides: :Na[O3S2R] + NaSR' -> RSSR' + Na2SO3
Reactions The most important aspect of disulfide bonds is their scission, as the bond is usually the weakest bond in an organic molecule. Many specialized
organic reactions have been developed to cleave the bond. A variety of reductants reduce disulfides to
thiols. Hydride agents are typical reagents, and a common laboratory demonstration "uncooks" eggs with
sodium borohydride. Alkali metals effect the same reaction more aggressively: RS-SR + 2 Na -> 2 NaSR, followed by protonation of the resulting metal thiolate: NaSR + HCl -> HSR + NaClIn biochemistry labwork, thiols such as β-
mercaptoethanol (β-ME) or
dithiothreitol (DTT) serve as reductants through
thiol-disulfide exchange. The thiol reagents are used in excess to drive the equilibrium to the right: RS-SR + 2 HOCH2CH2SH HOCH2CH2S-SCH2CH2OH + 2 RSH The reductant
tris(2-carboxyethyl)phosphine (TCEP) is useful, beside being odorless compared to β-ME and DTT, because it is selective, working at both alkaline and acidic conditions (unlike DTT), is more hydrophilic and more resistant to oxidation in air. Furthermore, it is often not needed to remove TCEP before modification of protein thiols. In Zincke cleavage, halogens oxidize disulfides to a
sulfenyl halide:ArSSAr + Cl2 -> 2 ArSClMore unusually, oxidation of disulfides gives first
thiosulfinates and then
thiosulfonates: :RSSR + [O] → RS(=O)SR :RS(=O)SR + [O] → RS(=O)2SR
Thiol-disulfide exchange In thiol–disulfide exchange, a
thiolate group displaces one
sulfur atom in a disulfide bond . The original disulfide bond is broken, and its other sulfur atom is released as a new thiolate, carrying away the negative charge. Meanwhile, a new disulfide bond forms between the attacking thiolate and the original sulfur atom. Thiolates, not thiols, attack disulfide bonds. Hence, thiol–disulfide exchange is inhibited at low
pH (typically, below 8) where the protonated thiol form is favored relative to the deprotonated thiolate form. (The
pKa of a typical thiol group is roughly 8.3, but can vary due to its environment.) Thiol-disulfide exchange is an important process for the formation of the correct
disulfide bridges in proteins and to keep cysteine from unwanted oxidation during lab experiments.
Nomenclature and misnomers Thiosulfoxides are isomeric with disulfides, having the second sulfur branching from the first and not partaking in a continuous chain, i.e. >S=S rather than −S−S−. Compounds with three sulfur atoms, such as CH3S−S−SCH3, are called trisulfides. More extended species are well known, especially in rings. Disulfide is also used to refer to compounds that contain two sulfide (S2−) centers. The compound
carbon disulfide, CS2 is described with the structural formula i.e. S=C=S. This molecule is not a disulfide in the sense that it lacks a S-S bond. Similarly,
molybdenum disulfide, MoS2, is not a disulfide in the sense again that its sulfur atoms are not linked. Disulfide bonds are analogous but more common than related
peroxide,
thioselenide, and
diselenide bonds. Intermediate compounds of these also exist, for example thioperoxides such as
hydrogen thioperoxide, have the formula R1OSR2 (equivalently R2SOR1). These are isomeric to
sulfoxides in a similar manner to the above; i.e. >S=O rather than −S−O−. ==Inorganic disulfides==